树鼩异种移植模型的建立及免疫排斥机制的深入研究

Xenotransplantation is one of the most promising ways to overcome the shortage of donor organs. But the lack of an ideal animal model is the most key problems at the same time, which can be used to study the complex mechanism of immune rejection of xenotransplantation. Tree shrew is low cost, small size, simple for transplant, and has a similarly immune system with people. Based on these characteristics, we establish the tree shrews xenotransplantation models innovatively, which include heart, kidney, pancreas transplantation model. Based on our existing research work, we explore the conditions of the model and feasibility, and study the mechanism of immune rejection by Omics, research and development of new immunosuppressant and strategies of tolerance induction, in order to strive for the long-term survival of xenograft and create a more ideal preclinical research platform of xenotransplantation. This project not only meet the national requirements to solve the problem of major disease treatment, but also drive the research in the field of xenotransplantation in China towards the international front, and cultivate a group of excellent talents, provide a solid theoretical basis and practical guidance for clinical xenotransplantation development.

异种移植是解决临床器官移植供体短缺的最有潜力的途径之一，但同时也面临一个最关键的问题，即缺乏一个理想的动物模型可以很好的研究异种移植复杂的免疫排斥机制。基于树鼩成本低、体型小、移植手术简单、免疫系统与人接近等特点，我们创新性地建立树鼩的异种心脏、肾、胰岛的移植模型，在已有的移植模型研究工作基础上，探索模型建立的条件及可行性，借助转录组学和代谢组学研究异种移植中免疫排斥的机制，研发新的免疫抑制剂与耐受诱导策略，争取实现异种移植物的长期存活，建立更理想的异种移植临床前研究平台。该项目不仅符合国家解决重大疾病治疗问题的需求，还将带动我国在异种移植领域的研究走向国际前沿，培养一批异种移植领域的优秀人才，为临床异种移植的开展提供坚实的理论基础和实践指导。

本课题旨在基于树鼩建立可替代非人灵长类动物的小型化、标准化的新型异种器官移植模型，在该模型基础上阐明树鼩异种移植模型的免疫排斥类型和机制，搭建新的异种移植研究平台。本课题组严格按照任务书要求开展相关研究工作，基本上建立和完善了树鼩的异种移植模型，并对该模型的解剖学参数、麻醉方法以及免疫排斥机制和类型进行了深入研究。此外，对大鼠到小鼠的异种移植模型、心脏移植、子宫移植等也进行了较好的研究，并尝试开发新型的免疫抑制剂。四年期间共发表 SCI 论文14篇，培养博士研究生5名、硕士研究生10名。总之，该课题开展了较多高质量的研究工作，搭建了较高水平的异种移植研究平台，为异种移植的研究培养了一直高水平的研究队伍，完成了预期目标。